Sequence Context Modulates the Stability of a GxxxG-mediated Transmembrane Helix–Helix Dimer

Transmembrane Segment 11 Appears to Line the Purine Permeation Pathway of the Plasmodium falciparum Equilibrative Nucleoside Transporter 1 (PfENT1)

“…1). GXXXG motifs are frequently found at sites of helix-helix interactions and are often important for protein folding and assembly (47)(48)(49)(50). We demonstrated that the polymorphism had functional effects of the adenosine and hypoxanthine K m .…”

Transmembrane domains of the syndecan family of growth factor coreceptors display a hierarchy of homotypic and heterotypic interactions

“…This selectivity of syndecan-1 heteromeric interactions shows that residues outside of the GxxxG must contribute to specificity. The role of sequence context in stabilizing helix-helix interactions mediated by a GxxxG motif has been studied quantitatively by Fleming and colleagues (46), who showed that single point mutations that leave the native GxxxG motif of GpA intact can modulate the free energy of dimerization in detergent micelles by Ϫ0.5 to ϩ3.2 kcal⅐mol Ϫ1 . We propose that the GxxxG motif permits close approach of syndecan transmembrane helices, but that the residues that flank the motif give rise to the distinct association properties of the four paralog TMDs.…”

A Dominant Negative Heterozygous G87R Mutation in the Zinc Transporter, ZnT-2 (SLC30A2), Results in Transient Neonatal Zinc Deficiency

“…the dimer interface to alanine contributes to dimerization, as alanine has a small side chain that can facilitate a closer approach of the transmembrane helices to maintain stronger van der Waals interactions (49). However, additional research is necessary to determine the definitive involvement of certain residues in the (F/Y)G(W/Y/F)XRXE signature in homodimerization.…”